Speaker
Description
We previously designed a competition assay with a collection of Staphylococcus aureus sRNA mutants to identify growth defects/advantages associated with sRNAs. We applied this assay to various conditions, including growth with a sublethal concentration of antibiotics, resulting in the identification of sRNAs associated with antibiotic tolerance. By subjecting the library to a medium containing sequestered iron, we identified IsrR-sRNA as being required for optimal growth when iron is unavailable. IsrR shows functional similarities to E. coli/Salmonella RyhB sRNA. It down-regulates the translation of numerous mRNAs encoding iron-containing proteins. These include the citB mRNA encoding aconitase and the ccpE mRNA encoding the aconitase transcriptional activator. IsrR is the master regulator of a feedback loop controlling aconitase levels. Moreover, in an iron-depleted environment, aconitase, a moonlighting protein (as reported in other species), becomes an RNA-binding protein, ensuring its autoregulation and controlling other genes. Our results highlight complex regulations for adapting to iron shortage, a condition faced by a pathogen within the host. A part of these results was recently published. I will present the continuation of this work with the characterization of IsrR and aconitase targets, and the contribution of moonlighting proteins to bacterial adaptation to growth conditions.
